lassesen 3:58 pm on December 28, 2020  

DAO and Probiotics

A reader requested me to do a review of the literature on probiotics and DAO as a result of my post, The Dilemma of D-Lactate Free Probiotics. As background on why DAO is important for some people, see:

The purpose of this post is to focus on DAO (and not treating histamine issues).

Returning to DAO and probiotics, the news is not good:

  • “Rats that received oral C. butyricum or butyrate had reduced intestinal injury and plasma levels of DAO, LPS, and inflammatory cytokines.” [2020]
  • “Streptococcus thermophiles…decreased endotoxin (ET), D-lactate (D-LA) and diamine oxidase (DAO) content in serum. [2020]
  • ” the serum DAO activity and D-lactate concentration significantly increased by fluoride were also reduced (P < 0.05) by…Lactobacillus johnsonii [2020]
  • ” DAO, endotoxin and D-lactate levels were significantly reduced following chronic ethanol consumption.” [2019] — Have lots of alcohol to reduce D-lactate!
  • “the Lactobacillus plantarum group exhibited reduced serum levels of diamine oxidase (DAO) compared with the p-control group” [2019]
  • ” Bacillus amyloliquefaciens …  significantly decreased activity of DAO compared with aureomycin group. [2018]
  • “Bifidobacterium or Lactobacillus … reduced plasma DAO and D-lactate. [2014]

The latest incursions into the probiotic market of claims have posited the amelioration of oxidative stress via potent antioxidant attributes or limiting the administration of probiotics to those species that do not produce D-Lactic acid (i.e., claims that D-Lactic acid acidosis is linked to chronic health conditions)..there is no place in science and medicine that supports unsubstantiated claims. Extravagant industry based notions continue to fuel the imprimatur of distrust and skepticism that is leveled by scientists and clinicians at an industry that is already rife with scientific and medical distrust and questionable views on probiotics. 

Probiotics, D-Lactic acidosis, oxidative stress and strain specificity [2017]

Histamine Intolerance: The Current State of the Art [2020] is a very informative read

  • “DAO (EC 1.4.3.22), also called histaminase or amiloride-binding protein, is a copper-dependent amino oxidase encoded by the AOC1 gene located on chromosome 7 (7q34-36) [14,15,16]. ” – so raising copper levels above average may be helpful (but not in excess).
    • Note that this refers to KEGG Enzyme, a recent addition to the Microbiome Prescriptions – alas, none of the bacterias or fungi associated with this is reported in current uploads.
  • There is an alternative,  histamine-N-methyltransferase (HNMT). “Thus, depending on its location, the histamine present in the body is deaminated or methylated by the action of the enzymes DAO and HNMT, respectively “
    • ” Histamine N-methyltransferase (HNMT) is a histamine-metabolising enzyme expressed in the brain…Clinical studies have suggested that single nucleotide polymorphisms of the human HNMT gene are associated with several brain disorders such as Parkinson’s disease and attention deficit hyperactivity disorder. ” [2019]
  • ” DAO deficiency has also been linked to certain functional gastrointestinal disorders, such as carbohydrate malabsorption and nonceliac gluten sensitivity (NCGS) [63,73,77,78,79]. “
  •  It has been estimated that approximately 20% of the European population regularly take DAO-inhibiting drugs, which significantly increases the number of people susceptible to the adverse effects of dietary histamine [28]

This article gives a nice, high level summary

Fruits, Fresh Meat, and Legumes are the safest

It is important to note that not only probiotics can reduce DAO levels, but many common supplements can too:

Vitamin B1 and Vitamin C should be avoided with histamine issues

Bottom Line

Avoid probiotics unless there is a very compelling reason to use them (i.e. solid studies), Vitamin B1 and Vitamin C. Radical ways to improve DAO levels: lots of fluoride and alcohol (not recommended).

IMHO, the promoter of the probiotics products claiming help for histamine is under a moral obligation to demonstrate with a study that they work. For these products, a study with 15 control and 15 with brain fog/high d-lactate by lab, is a very very low cost study. Take DAO and D-Lactate readings at start for all, give them the probiotics for 30-90 days, remeasure… then publish. BEAUTIFUL MARKETING MATERIAL. The absence of such publications strongly suggests that this is now pure marketing hype (based on a logical idea and being “sold” on logic and not on evidence based studies). For D-Lactate study likely was done with no (or negative) results – which is exactly what was reported in the study below [that did get published, likely because it was a registered trial].

“Open-label pilot for treatment targeting gut dysbiosis in myalgic encephalomyelitis/chronic fatigue syndrome: neuropsychological symptoms and sex comparisons’ 2018 – very similar product to below. “A small, negative correlation was observed between change in D:L lactate concentration ratios and change in Streptococcus count for the total sample (r s  = − .243, p = .142). ” This is NOT STATISTICALLY SIGNIFICANT ( p < 0.01 is what we want to see). 

Probiota Histiminix

This product claims ” contains probiotic species that have been carefully selected to exclude those that are known to increase histamine in the gut.” They omit to state that it probably decrease DAO. It contains:

  • Bifidobacterium infantis
  • Bifidobacterium bifidum
  • Bifidobacterium longum
  • Lactobacillus salivarius
  • Lactobacillus plantarum (study cited above states this species reduced DAO)
  • Bifidobacterium lactis
  • Bifidobacterium breve

Post Script for those with Histamine issues

This page may be useful, it includes how to check for DNA mutations that can result in low DAO or HNMT.

Addendum

Using KEGG for DAO and HNMT, we do find that DAO and HNMT are produced (i.e. have the genes to produce) by the following which are not technically probiotics (not bacteria), but are called such by some people.

  • Fungi
    • DAO
      • Ascomycetes
      • Basidiomycetes
      • Microsporidians
    • HNMT
      • Ascomycetes
      • Basidiomycetes
      • Microsporidians

Ascomycetes in both cases contains Saccharomycetes, and these specific strains (both available as a “probiotic” ):

There have been no studies of these on human histamine impact. There are reported allergic reaction (rare).

Feedback

A reader forward this image

Image may contain: text that says "Microorganisms capable of degrading histamine (DAO producers) Leuconostoc mesenteroides Leuconostoc sp. Escherichia faecium sp.group Sarcina lutea Lactobacillus curvatus Lactobacillus sakei Lactobacillus sp. Weisella hellenica Capable of degrading food sources of histamine and may reduce total histamine load Possible future role of probiotics? Dapkevicius.M Nout MJR, RomboutsF Houben JH, Wymenga W. ogenic amine format ion and degradat.ion by potential ish silage starter ganisms ntemationalj ouma Food Microbiology 2000 7:107 euschner Heidel Hammes N. Histamine and tyramine degradat Microbiology 1998 39:1-10 by ood er International of Food"

I looked at the sources of this information — food processing. Such studies are very very difficult to work from — because of murky causality. Is the observed change due to antibiotics produced by them inhibiting the bacteria producing histamines. We are also dealing with a very high oxygen environment (compare to the body). What we need to answer the questions are human studies…. where they are tested, is the effect an increase or decrease of DAO. So far (see above), lowering of DAO.